Pharmaceuticals

Diabetes is a serious, common and chronic health problem. In Canada, more than 2 million Canadians are living with diabetes today. Type 2 diabetes is the most common type of diabetes that accounts for approximately 90% of diabetes cases. The cost of diabetes care is almost 4 times as much as for someone without diabetes. The Canadian Diabetes Association estimates that the total cost of diabetes will continue to escalate and could reach $15.6 billion by 2010 unless dramatic actions are taken.

Vitamin D compounds are being developed for the treatment of chronic kidney disease. The purpose of this proposal is to develop a cell-based screening platform that will allow the rapid assessment ofrelative efficacy of a library of compounds. The intern will use recombinant DNA methodology to generate a cell-based assay in which the green fluorescence protein will be inserted into a vitamin D responsive gene; thus, permitting the visualization of vitamin D signaling in real-time.

The intern will use screening methods to define which gene which are altered in the Jurkat human T cell line following incubation with the Verotoxin B subunit as a means to define the potential mechanism by which this treatment protects these cells from HIV1 infection in vitro. LISI Therapeutics will benefit by increasing their license portfolio to include the rights of Verotoxin B subunit as a potential clinical treatment for HIV/AIDS.

The intern will generate DNA sequences to make modified verotoxin proteins that will effectively disrupt the breakdown of a mutant protein (the CFTR protein) that is found in patients with cystic fibrosis. The mutant CFTR protein has normal function but is degraded in cystic fibrosis individuals because of the mutation. The modified verotoxin will reduce the breakdown of the CFTR protein, and hence increase expression of the mutant CFTR protein and subsequent restoration of normal function of cells expressing CFTR protein.

Amorfix Life Sciences has had success producing highly specific antibodies, which can be used to diagnose disease. The company has recently gained access to an algorithm (ProMISTM) which allows to predict antibody targets on proteins in their diseased state, allowing development of very specific antibodies with diagnostic and therapeutic potential. The proposed project involves a comprehensive approach of identifying suitable protein targets involved in disease for the new algorithm by extensive database and market report mining.

Nosocomial infection is a growing problem in Canadian hospitals, these bacteria can kill as many as 8,000 patients per year, and the expenses reach at least $100 million annually. Clostridium difficile (C. difficile) and methicillin‐resistant Staphylococcus aureus (MRSA) are among the most common bacteria. For example, C. difficile has killed more than 600 people in Quebec alone between 2003 and 2005. The control of the spread of bacteria to multiple patients in hospitals and the efficacy of treatment will be improved with early detection of bacteria.

Pharmaceuticals are among the most commonly used and important healthcare treatments in Canada. They are also the second largest single healthcare expenditure and are the fastest increasing healthcare expenditure. For employers, pharmaceuticals are the largest component of their health benefits package and employees cite drugs as being the most valuable part of their employer-funded health benefits.

Amphotericin B is the most effective, and frequently the only treatment available for a number of life-threatening diseases, including systemic fungal infections and visceral leishmaniasis. The drawbacks of today’s amphotericin B treatment are toxicity and the need to administer the drug intravenously in hospital settings. The need for intravenous administration is due to poor absorption of the drug following oral administration and greatly increases the costs of the therapy and complications associated with intravenous admnistration.

Remifentanil, an anesthetic that is administered intravenously during acoustic shock wave treatment for kidney stones, depresses a patient's ability to breathe and can lead to apnea. Respiration is normally detected via standard patient monitors which sound alarms in the event that the patient ceases to breathe for a given length of time. However, a physician or nurse often intervenes before the alarms sound and is able to prompt the patient to breathe properly. The decision to intervene includes visual observation of respiration conditions, and requires vigilant monitoring.

In partnership with Labopharm, a leading company in optimizing the performance of small molecule drugs, a complete pharmacokinetic (PK) study of three new formulations of a commercially available drug will be performed. This study will be conducted in order to choose the most appropriate formulation in terms of bioavailability and absorption rate. Pharmacokinetics parameters of the drug will be estimated using different methods. Mechanisms of drug absorption, distribution, and elimination will also be identified.